ORGANIC
LETTERS
2006
Vol. 8, No. 10
1979-1982
Catalytic C−H Arylation of
SEM-Protected Azoles with Palladium
Complexes of NHCs and Phosphines
B. Barry Toure´, Benjamin S. Lane, and Dalibor Sames*
Department of Chemistry, Columbia UniVersity, 3000 Broadway,
New York, New York 10027
Received December 13, 2005
ABSTRACT
The synthesis and catalytic evaluation of palladium complexes containing imidazolyl carbene ligand of varying steric and electronic properties
is reported. These complexes catalyze the efficient C H arylation of SEM-protected azole heteroarenes and thus provide a good method for
−
preparation of a wide range of arylated free (NH)-azoles including pyrroles, indoles, imidazoles, and imidazo[1,2-a]pyridines. The reaction is
operationally simple; the complexes are insensitive to moisture.
Azoles are ubiquitous features of natural products, pharma-
ceuticals, and fluorescent dyes, as well as many other
synthetics. This broad range of uses of azoles and related
heteroarenes warrants the development of efficient and cost-
effective methods for their elaboration. The recent advances
in transition metal catalysis have unlocked many exciting
opportunities in this arena. New synthetic strategies such as
the direct functionalization of sp2 C-H bonds are now
emerging as viable alternatives to traditional cross-coupling
reactions.1 In these instances, the need for preactivating one
of the reaction components as its halide, tin, silicon, or boron
derivative is thus circumvented. The current repertoire
includes catalytic systems for arylation of 1-alkyl/aryl azoles
and binuclear azoles.2,3 However, the direct arylation of free
(NH)-azoles still remains a significant synthetic challenge.
Currently, there are two approaches to this problem: (1)
arylation of azole magnesium4 and zinc salts5 formed in situ
and (2) direct rhodium-catalyzed arylation of free (NH)-
pyrroles and indoles.6 While the former method suffers from
significant moisture sensitivity, the latter one is limited in
scope, most notably it is not applicable to imidazoles and
pyrrazoles.6 A new method for C-2 arylation of benzimida-
zole and related systems has been reported.7
We have recently reported a practical palladium-catalyzed
arylation of 1-alkyl indoles.2 A major drawback of this
procedure was the formation of biphenyl byproducts, which
was marginalized by using low catalyst loading. Although
satisfactory in the context of simple alkyl indoles, many
attractive but less reactive substrates such as SEM-protected
(1) Miura, M.; Nomura, M. Top. Curr. Chem. 2002, 219, 211-241.
(2) Lane, B. S.; Sames, D. Org. Lett. 2004, 6, 2897-2900.
(3) (a) Pivsa-Art, S.; Satoh, T.; Kawamura, Y.; Miura, M.; Nomura, M.
Bull. Chem. Soc. Jpn 1998, 71, 467-473. (b) Li, W. J.; Nelson, D. P.;
Jensen, M. S.; Hoerrner, R. S.; Javadi, G. J.; Cai, D.; Larsen, R. D. Org.
Lett. 2003, 4835-4837. (c) Park, C.-H.; Ryabova, V.; Seregin, I. V.;
Sromek, A. W.; Gevorgyan, V. Org. Lett. 2004, 6, 1159-1162. (d) Bellina,
F.; Cauteruccio, S.; Mannina, L.; Rossi, R.; Viel, S. J. Org. Chem. 2005,
70, 3997-4005.
(4) Lane, B. S.; Brown, M. A.; Sames, D. J. Am. Chem. Soc. 2005, 127,
8050-8057.
(5) Rieth, R. D.; Mankad, N. P.; Calimano, E.; Sadighi, J. P. Org. Lett.
2004, 6, 3981-3983.
(6) Wang, X.; Lane, B. S.; Sames, D. J. Am. Chem. Soc. 2005, 127,
4996-4997.
(7) Lewis, J. C.; Wiedemann, S. H.; Bergman, R. G.; Ellman, J. A. Org.
Lett. 2004, 6, 35-38.
10.1021/ol053021c CCC: $33.50
© 2006 American Chemical Society
Published on Web 04/12/2006